Those two B747-100 that were used to transport the space shuttle were extensively modified. The entire main cabin was stripped and replaced with strong struts to carry the load from the Space Shuttle directly down to the wing spars. They even added vertical stabilizers to increase stability and escape hatches for the crew. The first flights were carried out by the best test pilots in the world, some of whom had been to the moon. So even though all their models and calculations showed that it would work they were prepared for anything going wrong.
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